The demand for biosensors is increasingly growing these days. Usually, biosensors allow for the detection of a given specific molecule within an analyte, wherein the amount or concentration of said target molecule is typically small. For example, the amount of drugs or cardiac markers within saliva or blood may be measured. Drugs-of-abuse are generally small molecules that only possess one epitope and for this reason cannot be detected, e.g., by a sandwich assay. A competitive or inhibition assay is a preferred method to detect these molecules. A well-known competitive assay setup is to couple the target molecules of interest onto a surface, and link antibodies to a label or detection tag, that may be an enzyme, a fluorophore or magnetic beads. This system is used to perform a competitive assay between the target molecules from the sample and the target molecules on the surface, using the tagged antibodies. For road-side testing, the assay should be fast and robust.
In a magnetic-label biosensor, measuring the presence of certain biochemical agents such as drugs or cardiac markers is based on molecular capture and labeling with magnetic particles or beads. Magnetic attraction of the beads, also referred to as actuation, is essential in order to increase the performance, i.e. speed, of the biosensor for point-of-care applications. The direction of the magnetic attraction can be either towards the surface where the actual measurement is carried out or away from this surface. In the first case magnetic actuation allows the enhancement of concentration of magnetic particles near the sensor surface, speeding up the binding process of the magnetic particles at the sensitive surface. In the second case particles are removed from the surface which is called magnetic washing. Magnetic washing can replace the traditional wet washing step. It is more accurate and reduces the number of operating actions.
In a typical set-up of a magnetic biosensor device such as a biosensor device based on Frustrated Total Internal Reflection (FTIR), the magnetic beads are arranged in a sensor chamber of a sensor cartridge. At least a portion of a sensor surface in the sensor chamber is prepared for the detection of the target molecules. For performing the test, the cartridge is placed in a reader comprising magnetic units for generating a magnetic field at the sensor surface, and detection means for detecting the presence of magnetic beads near the sensor surface. To increase the reaction speed of the target molecules in a liquid which is inserted into the cartridge, the magnetic units arranged below the cartridge generate a magnetic field to pull the beads towards the sensor surface when cartridge is placed in the reader.
Due to magnetic attraction, the number of magnetic beads near the sensor surface of the biosensor device increases and the sensor signal increases in time. To attract the particles to the surface, a so-called pulsed magnetic attraction schedule may be used. In such a scheme, the magnetic field is periodically switched on and off as described for example in WO 2008/102218 A1. When the magnetic field is on, beads are attracted towards a region close to the surface. When the magnetic field is switched off, beads will diffuse towards the surface or away from the surface, depending of their original position. It is generally observed during measurements that during such a pulsed attraction scheme the signal near the center of the attraction magnet increases more rapidly than the signal near one of the poletips of the magnet.
This effect slows down the overall speed of the assay because the speed is dominated by the positions near the poletips. In practice, this problem can be circumvented by only using a few positions or Regions-Of-Interest near the center of the magnet. This is not a limitation in the case that only one type of target molecules has to be measured. However, for multi-analyte assays or multi-chamber configurations this is a limitation.